Citation: European Journal of Cancer Supplements, Vol 7 No 2, September 2009, Page 335

F. Di Fabio¹, C. Pinto¹, E. Maiello², S. Pini¹, T. Latiano², C. Aschele³, C. Garufi⁴, A. Bochicchio⁵, D. Tassinari⁶, A. Martoni<sup>1

1</sup>Medical Oncology Unit, S. Orsola-Malpighi Hospital, Bologna, Italy
²Medical Oncology Unit, IRCCS Casa Sollievo della Sofferenza, S. Giovanni Rotondo (FG), Italy
³Medical Oncology Unit, Galliera Hospital, Genoa, Italy
⁴Medical Oncology Unit, Regina Elena Institute, Rome, Italy
⁵Medical Oncology Unit, CROB, Rio Nero in Vulture (PZ), Italy
⁶Medical Oncology Unit, Degli Infermi Hospital, Rimini, Italy

Background: The aim of this phase II study was to assess the activity of preoperative external radiotherapy combined with panitumumab, oxaliplatin and 5-fluorouracil in locally advanced rectal cancer patients (pts).
Materials and Methods: Pts entering the study had histologically-proven rectal adenocarcinoma, either cT3N+ or cT4N-/+ stage, with location <12 cm from the anal margin. Panitumumab was administered at a dose of 6 mg/kg IV, 2 weeks before the start of chemoradiotherapy, and then in combination with chemoradiotherapy, 3 times every 2 weeks. 5-fluorouracil and oxaliplatin were administered according to established schedule of STAR-01 Study (oxaliplatin 60 mg/m² IV weekly six times, 1 h after the panitumumab infusion, and 5-fluorouracil 225 mg/m²/day continuous infusion IV days 1–38). Radiotherapy was delivered at a dose of 50.4 Gy in daily fractions of 1.8 Gy. Rectal surgery was performed 7–8 weeks after the end of neoadjuvant treatment. Eight courses of adjuvant chemotherapy with FOLFOX4 plus panitumumab at the dose of 6 mg/kg, every 2 weeks, were given post-surgery. The main study endpoint was complete pathological response rate.
Results: From February 2007 to April 2009 fifty-one pts were enrolled (9 too early pts). Characteristics of the 42 evaluated pts were: male 28 (66.7%), female 14 (33.3%); median age 60 (37–78); median Karnofsky PS 100 (70–100); stage: cT3N+ 31 (73.8%), cT4N- 3 (7.1%), cT4N+ 8 (19.1%). Thirty-three pts have completed neoadjuvant treatment and 30 have undergone surgery (12 pts ongoing). The most frequent grade 1–2 side effects were acneiform rash (56.7%), diarrhea (27%) and fatigue (8%). Grade 3–4 diarrhea was found in 32.4% of pts, and grade 3 cutaneous toxicity in 43.3%. No grade 3 hematological toxicity was found. The median cumulative dose of delivered radiotherapy was 50.4 Gy. The planned dose of panitumumab, 5-fluourouracil and oxaliplatin was administered in 78.8%, 63.6% and 69.6% of pts, respectively.
Conclusions: These early results demonstrate that panitumumab can be added to 5-fluorouracil/oxaliplatin-based chemoradiotherapy without compromising the concurrent radiotherapy dose. This combination treatment is associated with high incidence of grade 3–4 diarrhea.